Asthma and chronic obstructive pulmonary disease (COPD) together affect 300 million individuals worldwide. The major source of morbidity and mortality from both diseases is airway obstruction, which often is due to actively constricted smooth muscle of the bronchi/bronchial tree1. Although airway resistance in COPD has variable degrees of reversibility due to structural changes from smoking, therapies for COPD and asthma both include antagonists directed to broncho-constrictive receptors, and agonists directed to receptors that relax airway smooth muscle (ASM)2,3.
The major receptor signaling family of ASM that regulates contraction and relaxation are G-protein coupled receptors (GPCRs)3. There is an ongoing effort to identify GPCR pathways leading to regulation of airway tone, thereby providing for new treatment strategies for asthma and COPD. Such efforts are needed because the incidence of both diseases is increasing and at least one-half of all patients are not well controlled with currently available agents4,5.
There is an unmet need for additional therapeutic options in the treatment of obstructive airway diseases such as asthma and COPD. While there has been some progress in refining drugs that antagonize a particular Gq-coupled pathway, thereby potentially decreasing bronchospasm, β-agonists remain the only practical direct bronchodilators. The discovery and development of new means for treating obstructive lung diseases, such as asthma and COPD, are urgently needed.